National Cancer Institute

at the National Institutes of Health

Thyroid Cancer Treatment (PDQ®)

General Information About Thyroid Cancer

Incidence and Mortality

Estimated new cases and deaths from thyroid cancer in the United States in 2015:[1]

New cases: 62,450.

Deaths: 1,950.

Carcinoma of the thyroid gland is an uncommon cancer but is the
most common malignancy of the endocrine system.[2] Differentiated tumors
(papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumors (medullary or anaplastic) are much less common, are
aggressive, metastasize early, and have a much poorer prognosis. Thyroid
cancer affects women more often than men and usually occurs in
people between the ages of 25 and 65 years. The incidence of this malignancy has
been increasing over the last decade. Thyroid cancer commonly presents
as a cold nodule. The overall incidence of cancer in a cold nodule is 12% to
15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[3,4]

Risk Factors

Patients with a history of radiation administered in infancy and childhood for
benign conditions of the head and neck, such as enlarged thymus, acne, or
tonsillar or adenoidal enlargement, have an increased risk of cancer as well as
other abnormalities of the thyroid gland. In this group of patients,
malignancies of the thyroid gland first appear beginning as early as 5 years
following radiation and may appear 20 or more years later.[5] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[6-8] Other risk
factors for the development of thyroid cancer include the following:[9]

A history of goiter.

Family history of thyroid disease.

Female gender.

Asian race.

Prognostic Factors

The prognosis for differentiated
carcinoma is better for patients younger than 40 years without
extracapsular extension or vascular invasion.[10-14] Age appears to be the
single most important prognostic factor.[12] The prognostic significance of lymph node status is controversial. One
retrospective surgical series of 931 previously untreated patients with
differentiated thyroid cancer found that female gender, multifocality, and
regional node involvement are favorable prognostic factors.[15] Adverse factors
included age older than 45 years, follicular histology, primary tumor larger than 4
cm (T2–T3), extrathyroid extension (T4), and distant metastases.[15,16]
Other studies, however, have shown that regional lymph node involvement had no
effect [17,18] or even an adverse effect on survival.[13,14,19] Use of sentinel lymph node biopsy may aid in identifying patients with occult metastases who might benefit from central neck dissection.[20]

Risk factors and survivorship

Diffuse, intense
immunostaining for vascular endothelial growth factor in patients with
papillary cancer has been associated with a high rate of local recurrence and
distant metastases.[21] An elevated serum thyroglobulin level correlates
strongly with recurrent tumor when found in patients with differentiated
thyroid cancer during postoperative evaluations.[22,23] Serum thyroglobulin
levels are most sensitive when patients are hypothyroid and have elevated serum
thyroid-stimulating hormone levels.[24] Expression of the tumor suppressor
gene p53 has also been associated with an adverse prognosis for patients with
thyroid cancer.[25]

Low-risk factors

Patients considered at low risk by the age, metastases, extent, and size
(AMES) risk criteria include women younger than 50 years and men younger
than 40 years without evidence of distant metastases. Also included in
the low-risk group are older patients with primary tumors smaller than 5
cm and papillary cancer without evidence of gross extrathyroid
invasion or follicular cancer without either major capsular invasion or blood
vessel invasion.[11] Using these criteria, a retrospective study of 1,019
patients showed that the 20-year survival rate is 98% for low-risk patients and
50% for high-risk patients.[11] The 10-year overall relative survival rates for patients in the United States are 93% for papillary cancer, 85% for follicular cancer, 75% for medullary cancer, and 14% for undifferentiated/anaplastic cancer.[2]

The
thyroid gland may occasionally be the site of other primary tumors, including
sarcomas, lymphomas, epidermoid carcinomas, and teratomas and may be the site
of metastasis from other cancers, particularly of the lung, breast, and kidney.

Related Summaries

Other PDQ summaries containing information related to thyroid cancer include the following:

Cellular Classification of Thyroid Cancer

Cell type is an important determinant of prognosis in thyroid cancer. There
are four main varieties of thyroid cancer (although, for clinical management of
the patient, thyroid cancer is generally divided into two categories: well differentiated or
poorly differentiated):[1]

Papillary carcinoma.

Papillary/follicular carcinoma.

Follicular carcinoma.

Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.[2,3]

Medullary carcinoma.

Anaplastic carcinoma.

Small cell carcinoma.

Giant cell carcinoma.

Others.

Lymphoma.

Sarcoma.

Carcinosarcoma.

A definition for each major type can be found under stage information.

Papillary and Follicular Thyroid Cancer

Stage I papillary thyroid cancer

Stage I papillary carcinoma is localized to the thyroid gland. In as many as
50% of cases, there are multifocal sites of papillary adenocarcinomas throughout
the gland. Most papillary cancers have some follicular elements, and these may
sometimes be more numerous than the papillary formations, but this does not
change the prognosis. The 10-year survival rate is slightly better for
patients younger than 45 years than for patients older than 45 years.

Stage II papillary thyroid cancer

Stage II papillary carcinoma is defined as either: (1) tumor that has spread
distantly in patients younger than 45 years, or (2) tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
than 45 years. In as many as 50% to 80% of cases, there are multifocal
sites of papillary adenocarcinomas throughout the gland. Most papillary
cancers have some follicular elements, and these may sometimes be more numerous
than the papillary formations, but this does not appear to change the
prognosis.

Stage III papillary thyroid cancer

Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has
invaded adjacent cervical tissue has a worse prognosis than tumors confined to
the thyroid.

Stage IV papillary thyroid cancer

Stage IV is papillary carcinoma in patients older than 45 years with
extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent distant sites of
spread, though such distant spread is rare in this type of thyroid cancer.
Papillary carcinoma more frequently metastasizes to regional lymph nodes than
to distant sites. The prognosis for patients with distant metastases is poor.

Stage I follicular thyroid cancer

Stage I follicular carcinoma is localized to the thyroid gland. Follicular
thyroid carcinoma must be distinguished from follicular adenomas, which are
characterized by their lack of invasion through the capsule into the
surrounding thyroid tissue. While follicular cancer has a good prognosis, it
is less favorable than that of papillary carcinoma. The 10-year survival is better for
patients with follicular carcinoma without vascular invasion than it is for
patients with vascular invasion.

Stage II follicular thyroid cancer

Stage II follicular carcinoma is defined as either tumor that has spread
distantly in patients younger than 45 years, or tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
than 45 years. The presence of lymph node metastases does not worsen
the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from
follicular adenomas, which are characterized by their lack of invasion through
the capsule into the surrounding thyroid tissue. While follicular cancer has
a good prognosis, it is less favorable than that of papillary carcinoma; the
10-year survival is better for patients with follicular carcinoma without vascular
invasion than for patients with vascular invasion.

Stage III follicular thyroid cancer

Stage III is follicular carcinoma in patients older than 45 years, larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Follicular carcinoma invading
cervical tissue has a worse prognosis than tumors confined to the thyroid
gland. The presence of vascular invasion is an additional poor prognostic
factor. Metastases to lymph nodes do not worsen the prognosis in patients younger than 45 years.

Stage IV follicular thyroid cancer

Stage IV is follicular carcinoma in patients older than 45 years with
extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread.
Follicular carcinomas more commonly have blood vessel invasion and tend to
metastasize hematogenously to the lungs and to the bone rather than through the
lymphatic system. The prognosis for patients with distant metastases is poor.

Hürthle cell carcinoma

Hürthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and should be treated in the same way as equivalent stage non-Hürthle cell follicular carcinoma.[2]

Medullary Thyroid Cancer

Several staging systems have been employed to correlate extent of disease with
long-term survival in medullary thyroid cancer. The clinical staging system of
the AJCC correlates survival to size of the primary tumor, presence or absence
of lymph node metastases, and presence or absence of distance metastasis.
Patients with the best prognosis are those who are diagnosed by provocative
screening, prior to the appearance of palpable disease.[3]

Tumor larger than 2 cm but 4 cm or smaller with no metastases or larger than 4 cm with minimal extrathyroid extension.

Stage III medullary thyroid cancer

Tumor of any size with metastases limited to the pretracheal, paratracheal, or prelaryngeal/Delphian lymph nodes.

Stage IV medullary thyroid cancer

Stage IV medullary thyroid cancer is divided into the following categories:

Stage IVA (moderately advanced with or without lymph node metastases [for T4a] but without distant metastases).

Stage IVB (very advanced with or without lymph node metastases but no distant metastases).

Stage IVC (distant metastases).

Medullary carcinoma usually presents as a hard mass and is often accompanied
by blood vessel invasion. Medullary thyroid cancer occurs in two forms,
sporadic and familial. In the sporadic form, the tumor is usually unilateral.
In the familial form, the tumor is almost always bilateral. In addition, the
familial form may be associated with benign or malignant tumors of other
endocrine organs, commonly referred to as the multiple endocrine neoplasia
syndromes (MEN 2A or MEN 2B).

In these syndromes, there is an association with pheochromocytoma of the adrenal
gland and parathyroid hyperplasia. Medullary carcinoma usually secretes
calcitonin, a hormonal marker for the tumor, and may be detectable in blood
even when the tumor is clinically occult. Metastases to regional lymph nodes
are found in about 50% of cases. Prognosis depends on extent of disease at
presentation, presence or absence of regional lymph node metastases, and
completeness of the surgical resection.[4]

Family members should be screened for calcitonin elevation to identify
individuals who are at risk of developing familial medullary thyroid cancer.
MEN 2A gene carrier status can be more accurately determined by analysis of
mutations in the RET gene. Whereas modest el
mutation is the optimal approach in evaluating MEN 2A. All patients with
medullary carcinoma of the thyroid (whether familial or sporadic) should be
tested for RET mutations, and, if they are positive, family members should
also be tested. Family members who are gene carriers should undergo
prophylactic thyroidectomy at an early age.[5-7]

Anaplastic Thyroid Cancer

No generally accepted staging system is available for anaplastic thyroid cancer.
All patients are considered to have stage IV disease.

Undifferentiated (anaplastic) carcinomas are highly malignant cancers of
the thyroid. They may be subclassified as small cell or large cell carcinomas.
Both grow rapidly and extend to structures beyond the thyroid. Both small cell
and large cell carcinomas present as hard, ill-defined masses, often with
extension into the structures surrounding the thyroid. Small cell anaplastic
thyroid carcinoma must be carefully distinguished from lymphoma. This tumor
usually occurs in an older age group and is characterized by extensive local
invasion and rapid progression. Five-year survival with this tumor is poor.
Death is usually from uncontrolled local cancer in the neck, usually within
months of diagnosis.[8]

Stage I and II Papillary and Follicular Thyroid Cancer

Surgery is the therapy of choice for all primary lesions. Surgical options
include total thyroidectomy or lobectomy. The choice of procedure is
influenced mainly by the age of the patient and the size of the nodule.
Survival results may be similar; the difference between them lies in the rates
of surgical complications and local recurrences.[1-7]

Total Thyroidectomy

This procedure is advocated because of the high
incidence of multicentric involvement of both lobes of the gland and the
possibility of dedifferentiation of any residual tumor to the anaplastic cell
type.

From the National Cancer Center Data Base (NCDB) registry of 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8,946 (17.1%) underwent lobectomy. For a papillary thyroid cancer measuring less than 1 cm, the extent of surgery did not impact recurrence or survival (P = .24 and P = .83, respectively).[8] For tumors measuring 1 cm or larger, lobectomy resulted in higher risk of recurrence and death (P = .04 and P = .009, respectively). To minimize the influence of larger tumors, 1-cm to 2-cm lesions were examined separately; lobectomy again resulted in a higher risk of recurrence and death (P = .04 and P = .04, respectively). In this study, total thyroidectomy resulted in lower recurrence rates and improved survival for patients with papillary thyroid cancer measuring 1 cm or larger compared with lobectomy.[8][Level of evidence: 3iiA]

Furthermore, in a pattern of care study, using the NCDB registry from 1985 to 2003, 57,243 papillary thyroid cancer patients with tumors measuring 1 cm or larger underwent total thyroidectomy or lobectomy. Trends in the extent of surgery were examined for patients with papillary thyroid cancer over 2 decades. Logistic regression was used to identify factors that predict the use of total thyroidectomy compared with lobectomy. Use of total thyroidectomy increased from 70.8% in 1985 to 90.4% in 2003 (P < .0001). Patients treated at high-volume medical facilities or academic centers were more likely to undergo total thyroidectomy than were patients examined at low-volume medical facilities or community hospitals (P < .0001).[9][Level of evidence: 3i]

The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with radioactive iodine (RAI). The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning.

I131: Studies have shown that a postoperative course of therapeutic
(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary
and follicular carcinomas.[4] It may be given in addition to exogenous thyroid
hormone but is not considered routine.[10] Patients presenting with papillary
thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when
treated surgically, and additional therapy with I131 would not be expected to
improve the prognosis.[11]

Lobectomy

Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases. This procedure is associated with a lower incidence of
complications, but approximately 5% to 10% of patients will have a recurrence
in the thyroid following lobectomy.[12] Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for
recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I131 as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of
surgery. Recognized nodal involvement should be removed at initial surgery, but
selective node removal can be performed, and radical neck dissection is usually not
required.
This
results in a decreased recurrence rate but has not been shown to improve
survival.

Following the surgical procedure, patients should receive postoperative
treatment with exogenous thyroid hormone in doses sufficient to suppress
thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of
recurrence when TSH is suppressed.

I131: Studies have shown that a postoperative course of therapeutic
(ablative) doses of I131 results in a decreased recurrence rate among high-risk patients with papillary
and follicular carcinomas.[4] For optimal treatment with RAI, total thyroidectomy is recommended with minimal thyroid remnant remaining. With a large thyroid remnant, a low thyroglobulin level cannot be achieved, which increases the chance of requiring multiple doses of RAI.

Consideration of RAI for remnant ablation is based on pathological risk features including:

Evaluation of the size of the primary tumor.

The presence of lymphovascular invasion.

Capsule invasion.

The number of involved lymph nodes.

RAI may be given with one of two methods of thyrotropin stimulation: withdrawal of thyroid hormone or recombinant human thyrotropin (rhTSH). Administered rhTSH maintains quality of life and reduces the radiation dose delivered to the body compared with thyroid hormone withdrawal.[13] Patients presenting with papillary
thyroid microcarcinomas (tumors <10 mm), which are considered to be very low risk, have an excellent prognosis when
treated surgically, and additional therapy with I131 would not be expected to
improve the prognosis.[11]

The role of RAI in low-risk patients is not clear because disease-free survival (DFS) or overall survival (OS) benefits have not been demonstrated. One study reviewed 1,298 patients from the French Thyroid Cancer Registry.[14] Patients were identified as having low-risk papillary or follicular cancer as they are defined by the American Thyroid Association and the European Thyroid Association criteria:

Of the 1,298 patients, 911 patients received RAI after surgery, and 387 patients did not receive RAI after surgery. Follow-up period was 10.3 years; in multivariate analyses, there were no differences in OS (P = .243) or DFS (P = .2659), according to RAI use.[14]

Long-term complications of RAI using I131 include second malignancies, sialadenitis, and lacrimal and salivary gland dysfunction. Options for reducing the amount of radiation exposure by reducing the amount of RAI in each dose and also to give RAI in combination with rhTSH injections have been explored for low-risk thyroid cancer patients.

Two phase III, randomized, noninferiority studies of patients with low-risk thyroid cancer using a comparison of two thyrotropin-stimulation methods (thyroid hormone withdrawal or use of rhTSH) and two doses of radioiodine I131 1.1GBq [30mCi] and 3.7GBq [100mCi] using a 2 × 2 factorial design showed equivalent thyroid ablation rates between high and low dose I131 at 6 to 10 months after administration of I131.[15,16][Levels of evidence: 3iA and3iDii] However, differences in the inclusion criteria in one study [15] consisted of a low-risk, homogeneous cohort in which all of the patients underwent total thyroidectomy, and had pathological TNM stage pT1 ( ≤1 cm) and N1 or Nx, pT1 (>1–2cm) and any N stage, or pT2N0 without thyroid capsule extension/distant metastases. Complete thyroid ablation rate in this study was 92%. Patients undergoing thyroid hormone withdrawal had greater symptoms of hypothyroidism associated with deterioration in quality of life compared with the rhTSH group.

In the other study,[16] patients with more advanced T stage (T1–T3, N0–1) and with less than a total thyroidectomy were included with a lower overall ablation rate of 85%. Neither study assessed the effect of low-dose RAI on long-term recurrences or survival. The studies also did not address whether RAI could be safely omitted in specific low-risk groups.

Stage IV Papillary and Follicular Thyroid Cancer

The most common sites of metastases are lymph nodes, lung, and bone. Treatment
of lymph node metastases alone is often curative. Treatment of distant
metastases is usually not curative but may produce significant palliation.

Standard treatment options for iodine-sensitive thyroid cancer:

I131: Metastases that demonstrate uptake of this isotope may be ablated
by therapeutic doses of I131.

Standard treatment options for iodine-resistant thyroid cancer:

Thyroid-stimulating hormone suppression with thyroxine is effective in many
lesions not sensitive to I131.

Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; P = .14, one-sided P-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed.

Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; P < .001).

Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.

Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I131.

External-beam radiation therapy for patients with localized lesions that are
unresponsive to I131.[2]

Patients unresponsive to I131 should also be considered candidates for
clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

Clinical trials evaluating new treatment approaches to this disease should also
be considered for these patients. Chemotherapy has been reported to produce
occasional complete responses of long duration.[3-5] Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[6][Level of evidence: 2Dii]

Medullary Thyroid Cancer

Medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers.
These tumors usually present as a mass in the neck or thyroid, often associated
with lymphadenopathy,[1] or they may be diagnosed through screening family
members. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology
typically reveals hypercellular tumors with spindle-shaped cells and poor
adhesion.[2]

The overall survival of patients with MTC is 86% at 5 years and 65% at 10 years. Poor prognostic
factors include advanced age, advanced stage, prior neck surgery, and
associated multiple endocrine neoplasia (MEN) 2B.[2-4]

Approximately 25% of reported cases of MTC are familial.
Familial MTC syndromes include MEN 2A, which is
the most common; MEN 2B; and familial non-MEN syndromes. (Refer to the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.) Any patient with a
familial variant should be screened for other associated endocrine tumors,
particularly parathyroid hyperplasia and pheochromocytoma. MTC can secrete
calcitonin and other peptide substances. Determining the level of calcitonin
is useful for diagnostic purposes and for following the results of treatment.

Family members should be screened for calcitonin elevation and/or for the RET
proto-oncogene mutation to identify other individuals at risk for developing
familial MTC. All patients with MTC (whether familial or sporadic) should be
tested for RET mutations, and if they are positive, family members should
also be tested. Whereas modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the RET mutation is
the optimal approach. Family members who are gene carriers should undergo
prophylactic thyroidectomy at an early age.[5,6]

Thyroidectomy

Patients with MTC should be treated with a total
thyroidectomy, unless there is evidence of distant metastasis. In patients
with clinically palpable MTC, the incidence of
microscopically positive nodes is more than 75%; routine central and bilateral
modified neck dissections have been recommended.[7] When cancer is confined to
the thyroid gland, the prognosis is excellent.

External Radiation Therapy

External radiation therapy has been used for palliation of locally recurrent
tumors; however, no evidence exists that it provides any survival advantage.[8] Radioactive iodine has no place in the treatment of patients with MTC.

Overall survival (OS) was not different at 24 months; longer follow-up will be required since only 47 patients had died at the time of analysis, and there was a crossover to the study drug on progression from placebo, making analysis of OS problematic. Vandetanib has significant side effects, including diarrhea, rash, hypertension, and QT prolongation. Quality of life was not formally assessed in this trial.[9]

Palliative chemotherapy has been reported to produce occasional responses in
patients with metastatic disease.[10-13] No single drug regimen can be
considered standard. Some patients with distant metastases will experience
prolonged survival and can be managed expectantly until they become
symptomatic.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
thyroid gland medullary carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Anaplastic Thyroid Cancer

Surgery

Tracheostomy is frequently necessary. If the disease is confined to the local area, which is rare, total thyroidectomy is warranted to
reduce symptoms caused by the tumor mass.[1,2]

Radiation Therapy

External-beam radiation therapy may be used in patients who are not surgical candidates or whose tumor cannot be surgically
excised.

Chemotherapy

Anaplastic thyroid cancer is not responsive to I131 therapy;
treatment with individual anticancer drugs has been reported to produce partial
remissions in some patients. Approximately 30% of patients achieve a partial
remission with doxorubicin.[3] The combination of doxorubicin plus cisplatin
appears to be more active than doxorubicin alone and has been reported to
produce more complete responses.[4]

Treatment options under clinical evaluation:

The combination of chemotherapy plus radiation therapy in patients following complete
resection may provide prolonged survival but has not been compared with any one
modality alone.[5,6]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
anaplastic thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Recurrent Thyroid Cancer

Patients treated for differentiated thyroid cancer should be followed carefully
with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based
on individual risk for recurrent disease.[1] Approximately 10% to 30% of
patients thought to be disease free after initial treatment will develop
recurrence and/or metastases. Of these patients, approximately 80% develop recurrence
with disease in the neck alone, and 20% develop recurrence with distant metastases. The most
common site of distant metastasis is the lung. In a single series of 289
patients who developed recurrences after initial surgery, 16% died of cancer at
a median time of 5 years following recurrence.[2]

The prognosis for patients
with clinically detectable recurrences is generally poor, regardless of cell
type.[3] Those patients who recur with local or regional tumor
detected only by I131 scan, however, have a better prognosis.[4] The selection of
further treatment depends on many factors, including cell type, uptake of
I131, prior treatment, site of recurrence, and individual patient
considerations. Surgery with or without I131 ablation can be useful in
controlling local recurrences, regional node metastases, or, occasionally,
metastases at other localized sites.[5] Approximately 50% of the patients
operated on for recurrent tumors can be rendered free of disease with a second
operation.[3] Local and regional recurrences detected by I131 scan and not
clinically apparent can be treated with I131 ablation and have an excellent
prognosis.[6]

Up to 25% of recurrences and metastases from well-differentiated thyroid cancer
may not show I131 uptake. For these patients, other imaging techniques shown
to be of value include imaging with thallium-201, magnetic resonance imaging,
and pentavalent dimercaptosuccinic acid.[7] When recurrent disease does not
concentrate I131, or disease recurs after I131 ablation, sorafenib has been approved by the U.S. Food and Drug Administration as a treatment option.

Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; P = .14, one-sided P-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed.

Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; P < .001).

Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.

External-beam or intraoperative radiation therapy can be
useful in controlling symptoms related to local tumor recurrences.[9] Systemic
chemotherapy can be considered. Chemotherapy has been reported to produce
occasional objective responses, usually of short duration.[4,10]

Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

Clinical trials evaluating new treatment approaches to this disease should also
be considered for these patients. Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[11][Level of evidence: 2Dii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
recurrent thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Added text to state standard treatment options for iodine-resistant thyroid cancer include the option sorafenib, and added that a phase III randomized, double-blind, placebo-controlled study (DECISION) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor, in patients with progressive iodine-refractory differentiated thyroid cancer, and described the results of the trial, adding that prior chemotherapy, thalidomide, or targeted therapy were excluded (cited Brose et al. as reference 1 and level of evidence 1iDiii).

Revised text to state that when recurrent disease does not
concentrate I131, or disease recurs after I131 ablation, sorafenib has been approved by the U.S. Food and Drug Administration as a treatment option.

Revised text to state that a phase III randomized, double-blind, placebo-controlled study (DECISION) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor in patients with progressive iodine-refractory differentiated thyroid cancer, and described the results of the trial, adding that prior chemotherapy, thalidomide, or targeted therapy were excluded (cited Brose et al. as reference 8 and level of evidence: 1iDiii).

Added text to state that external-beam radiation therapy or intraoperative radiation therapy can be
useful in controlling symptoms related to local tumor recurrences (cited Vikram et al. as reference 9). Also added that systemic
chemotherapy can be considered; chemotherapy has been reported to produce
occasional objective responses, usually of short duration (cited Shimaoka et al. as reference 10).

Added text to state that patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Added text to include treatment options under clinical evaluation and stated that clinical trials evaluating new treatment approaches to this disease should also
be considered for these patients. Also added that oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation (cited Sherman et al. as reference 11 and level of evidence 2Dii).

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of thyroid cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

be discussed at a meeting,

be cited with text, or

replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Thyroid Cancer Treatment are:

Scharukh Jalisi, MD, FACS (Boston University Medical Center)

Eva Szabo, MD (National Cancer Institute)

Minh Tam Truong, MD (Boston University Medical Center)

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Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

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